Actin filaments are dynamic polymers whose assembly and disassembly in the cytoplasm drive shape changes [76], cell locomotion [77] and chemotactic migration [78]. The elongation of thefilament in the cell is accompanied by hydrolysis of adenosinetriphosphate (ATP), the fundamental carrier of metabolic energyin the cell [79]. We are interested in the role of waters and ions inactin's ATPase activity. We have carried out several MD calculations of the solvated protein (10,000 atoms, including about 1,200waters) for up to 500 ps of simulation time and have investigatedthe essential movements [7]. We found two water diffusion channels which we believe serve in the exchange of the metal ion andof nucleotide hydrolysis products. Of special interest is the "backdoor" diffusion pathway which may allow the release of inorganic phosphate and the exchange of the metal ion without dissociatingthe nucleotide. We plan to study further the dissociation of thenucleotide and the role of the proposed "back door" for actin's enzymatic activity by means of interactive modelling. If successful,this work will be the first computer simulation to model the exchange of substrates in an ATPase. The methodology developedand the resulting structural prediction of the dissociation mechanism may benefit research on other related enzymes such as thechaperone Hsc70, G-proteins, and ATP-driven motor proteins likemyosin and kinesin.